11-88291569-TGAAAGAAA-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000678554.1(CTSC):c.890-1070_890-1063del variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: 𝑓 0.18 (1986 hom., cov: 0)
• Consequence: CTSC ENST00000678554.1 intron, NMD_transcript
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 1.31

Genes affected

CTSC (HGNC:2528): (cathepsin C) This gene encodes a member of the peptidase C1 family and lysosomal cysteine proteinase that appears to be a central coordinator for activation of many serine proteinases in cells of the immune system. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate heavy and light chains that form a disulfide-linked dimer. A portion of the propeptide acts as an intramolecular chaperone for the folding and stabilization of the mature enzyme. This enzyme requires chloride ions for activity and can degrade glucagon. Defects in the encoded protein have been shown to be a cause of Papillon-Lefevre syndrome, an autosomal recessive disorder characterized by palmoplantar keratosis and periodontitis. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTSC	ENST00000678554.1	c.890-1070_890-1063del		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.177 AC: 22322 AN: 126086 Hom.: 1991 Cov.: 0

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.157

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.176

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.177 AC: 22322 AN: 126168 Hom.: 1986 Cov.: 0 AF XY: 0.182 AC XY: 10928 AN XY: 60154

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.364

Gnomad4 SAS AF: 0.239

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.174

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Department of Pathology and Laboratory Medicine, Sinai Health System

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs36141641; hg19: chr11-88024737;